In the context of dialysis and clearance of toxins, molecules such as Creatinine, Urea and Potassium are easy to clear because they are fairly small and pass easily through the membrane of the dialyzer or the artificial kidney. However, there are some bigger molecules such as Beta 2 Microglobulin. These molecules are very difficult to remove since they do not pass through the dialyzer membrane. It is important that these molecules be removed since they are also, after all, toxins and are harmful for the body.

There has been some discussion about how longer duration, more frequent dialysis removes the middle molecules more efficiently than the conventional modalities. I fail to understand how though.

Let's say you drill a hole in a wall about the size of a marble. Now, take a football and hit it against the hole. Will it go through? Obviously not! Now try again and again for a few hours. Will it make any difference? Obviously not!

This is very similar to the middle molecule scenario. The middle molecules simply cannot pass through the membranes of the regular dialyzers because the pore size is not big enough. The duration of dialysis cannot influence the result. Neither can the frequency. So, for a change, you have longer, more frequent dialysis as ineffective at achieving clearance of middle molecules as conventional dialysis.

How can we then clear middle molecules effectively?

High flux dialyzers. These dialyzers have bigger pore sizes and are the only way middle molecules can be cleared. Again, you will need more frequent, longer duration dialysis to be able to do this effectively. But high flux dialyzers really are the key.

This was also demonstrated in a study conducted in Australia outlined in this paper.